FDA Approval in Normal Times vs Emergencies

Getting a drug, vaccine, or medical device approved in the US can look confusing at first. But there is a clear method behind the process. Understanding these steps builds consumer trust. It also helps encourage people to join pre-clinical and clinical research studies.

How drugs are normally approved
When Americans buy medicine, or get a prescription from their doctor, they can trust that they benefit from one of the world’s safest and most advanced drug systems.

The Center for Drug Evaluation and Research (CDER), part of the Food and Drug Administration (FDA), plays a big role here. It evaluates new drugs before they reach the market. The center checks that drugs work as intended, and that their benefits outweigh their risks.¹

Drug companies first test the drugs they want to sell. They do this through pre-clinical and clinical trials, then submit the resulting data to the FDA. Physicians, statisticians, chemists, pharmacologists, and other CDER scientists review this data, along with any proposed labeling.¹

Companies can choose from 5 application types when submitting a drug for FDA approval: investigational new drug, new drug application, abbreviated new drug application, over-the-counter drugs, or a biologic license application.² (Go here for more on each application type.)

CDER uses a structured framework to review 3 key areas of each application:¹

• Analysis of the target condition and available treatment,
• Assessment of benefits and risks from clinical data
• Strategies for managing risks.

If CDER decides the benefits outweigh the risks, the drug gets FDA approval.¹ For consumers, the biggest hidden cost of this process may be time: drug approval can take 12 to 15 years.³

How vaccines are normally approved
Vaccine approval follows a similar process, but a different FDA center oversees it: the Center for Biologics Evaluation and Research (CBER). Vaccine developers typically start research and discovery in a lab, just like drug developers. Next comes animal testing in the pre-clinical phase, then testing in people during clinical development.⁴

While clinical testing continues, the FDA commonly checks how and where the vaccine is manufactured. Once the manufacturing process is confirmed reliable and consistent, and pre-clinical and clinical development are complete, vaccine companies submit a Biologics License Application to the FDA. This is how a company shares its pre-clinical data, clinical data, and manufacturing process with the FDA.⁴

A CBER team of physicians, statisticians, chemists, pharmacologists, toxicologists, microbiologists, and manufacturing inspectors then reviews the BLA application, focusing on safety and efficacy. After a vaccine gets FDA approval, post-market monitoring continues to watch for adverse events and long-term complications.⁴

What can be authorized for emergency use?
During certain public health emergencies, the FDA’s normal approval timelines can slow the government’s ability to deliver medical countermeasures (MCMs) to people who need them.⁵

MCMs are FDA-regulated products used in public health emergencies to diagnose, treat, prevent, or protect people from health conditions tied to national threats. MCMs include medicines (like anti-infectives or antidotes), devices (diagnostic tests or personal protective equipment), and biologics (vaccines, blood products, and antibody or cellular treatments).⁵

The FDA can allow use of an unapproved medical product, or a new, previously unapproved use of an approved medical product. In other words, they can speed up approval of a product that hasn’t gone through the normal review process, or approve a new use for a product already approved for something else (similar to approving off-label uses).⁵

The FDA supports MCM development by working with partners across all levels of government, plus non-governmental organizations and researchers from academia or industry.⁵

When can emergency authorization be used?
Public health emergencies that trigger an EUA can come from many sources, including chemical, biological, radiological, or nuclear attacks, and emerging infectious diseases.^5,6

Before the FDA can authorize drugs, vaccines, or other medical countermeasures under an EUA, the Secretary of the US Department of Health and Human Services must first declare that a threat, or potential threat, to public health exists. This requirement comes from section 564 of the Federal Food, Drug, and Cosmetic Act.⁶

What does the emergency use authorization process involve?
Depending on the specific national threat, MCMs may come from the strategic national stockpile (such as patient ventilators and provider personal protective equipment), or through special FDA approvals like the Emergency Use Authorization.⁷

The FDA’s guidelines for Emergency Use Authorization of Medical Products and Related Authorities define the conditions for issuing EUAs, and which products qualify.⁸

The FDA will only issue an EUA if all 4 of these conditions are met:⁸

• The health threat must be a serious or life-threatening disease or condition.
• There must be evidence the medical product “may be effective” at treating the disease or condition — this is a slightly lower bar than the effectiveness standard used for typical FDA approvals.
• The benefits of the medical product for diagnosing, preventing, or treating the disease or condition must outweigh the risks.
• There must be no other adequate, approved, or available alternatives.

To start the EUA process, an industry or government sponsor works with the FDA on medical products that could use an EUA, before submitting an application. These are called “pre-EUA activities,” meant to guide the submission process.⁸

EUA submissions should include:⁸

• Information about the product and its use,
• A description of the product’s FDA-approval status (if any),
• The need for the product,
• All available safety and efficacy data,
• A discussion of its risks and benefits,
• Information on its chemistry,
• Information on how much product is on hand and how fast more can be made during a surge in demand,
• Information similar to a package insert

The FDA reviews EUA submissions by priority, based on factors like how urgent the threat is, how urgently the treatment is needed, and the company’s ability to manufacture it.⁸

Companies can start a full approval submission under the normal process at the same time their product is being used under an EUA. When an EUA is no longer needed, it’s terminated or revoked, and a public record is kept.⁹

EUAs can play an important role in getting vaccines, antivirals, and new medical devices to the public faster than the traditional review process allows. But moving fast during a public health crisis doesn’t mean safety or efficacy get compromised. The EUA process still carefully evaluates safety and efficacy to protect consumers, while balancing the benefits and risks of making a drug, vaccine, or device available during a crisis.

References

1. US Food and Drug Administration. Development & Approval Process | Drugs. Available at https://www.fda.gov/drugs/development-approval-process-drugs. Accessed 8/27/21.
2. US Food and Drug Administration. How Drugs are Developed and Approved. Available at https://www.fda.gov/drugs/development-approval-process-drugs/how-drugs-are-developed-and-approved. Accessed 8/27/21.
3. com. FDA Drug Approval Process. Available at https://www.drugs.com/fda-approval-process.html. Accessed 8/27/21.
4. US Food and Drug Administration. Vaccine Development 101. Available at https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/vaccine-development-101. Accessed 8/27/21.
5. US Food and Drug Administration. What are Medical Countermeasures? Available at https://www.fda.gov/emergency-preparedness-and-response/about-mcmi/what-are-medical-countermeasures. Accessed 8/27/21.
6. US Food and Drug Administration. Emergency Use Authorization. Available at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization. Accessed 8/27/21
7. US Food and Drug Administration. MCM Emergency Use Authorities. Available at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/mcm-emergency-use-authorities. Accessed 8/27/21.
8. US Food and Drug Administration. Emergency Use Authorization of Medical Products and Related Authorities. Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/emergency-use-authorization-medical-products-and-related-authorities. Accessed 8/27/21.
9. US Food and Drug Administration. Emergency Use Authorization—Archived Information. Available at https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization-archived-information. Accessed 8/27/21.

Infographic available here:

FDA Emergency Use Authorization Infographic